Avoiding negative outcomes: tracking the mechanisms

The amygdala has been the focus of investigations of aversive learning, particularly Pavlovian fear conditioning paradigms in which fear is expressed passively, such as through autonomic responses (for review see Phelps and LeDoux, 2005). In contrast, the human striatum has been highlighted in investigations of reward-related processing, such as instrumental paradigms, that involve decision-making and action-contingencies (for review see Montague and Berns, 2002; O’Doherty, 2004; Knutson and Cooper, 2005; Delgado, 2007; Rangel et al., 2008). The human striatum, however, is also implicated in aversive learning (e.g., Jensen et al., 2003; Seymour et al., 2004, 2007; Menon et al., 2007; Delgado et al., 2008a). Studies from non-human animals have led to the hypothesis that one role for the striatum in aversive learning may be to aid in the acquisition of avoidance actions that diminish exposure to a fear-eliciting event (LeDoux and Gorman, 2001). For example, an investigation in rodents examining the amygdala subnuclei that mediate fear-motivated action found that the basal nucleus, which projects to the striatum (Mogenson et al., 1980; Robbins et al., 1989), is necessary for the acquisition of a fear-reducing action, but is not necessary for more passive expressions of conditioned fear (Amorapanth et al., 2000). In contrast, the central nucleus, which projects to the brainstem and hypothalamus, is necessary for the passive expression of fear, but not for learning a fear-reducing action. These results suggest that INTRODUCTION The ability to modify and control our emotional responses is c ritical for adaptive function and goal-directed behavior. Although learning to fear a potentially dangerous situation is important, it is equally important to be able to modify this fear when new information is available, or use this fear to motivate adaptive action that diminishes the potential threat. Recent research examining the neural systems of regulating fear in humans has highlighted passive extinction techniques (Milad and Quirk, 2002; Knight et al., 2004; Phelps et al., 2004) and the use of cognitive strategies (Kalisch et al., 2005; Ochsner and Gross, 2005; Delgado et al., 2008b). These techniques focus on modifying the fear response in the presence of the fear-eliciting event. Another common response used to regulate fear, however, is to take an action to avoid the potential danger and diminish the fear response. Given how frequently action is used to cope with potential threat and fear outside the laboratory, surprisingly little research conducted in humans has examined the neural system mediating the active coping of fear. Research in non-human animals has suggested that active coping of fear may involve amygdala and striatal interactions (Killcross et al., 1997; Everitt et al., 1999; LeDoux and Gorman, 2001; Cardinal et al., 2002). The goal of the present study is to investigate if an amygdala–striatal circuitry underlies active coping of fear in humans. Avoiding negative outcomes: tracking the mechanisms of avoidance learning in humans during fear conditioning